Thebaine is an opiate alkaloid. While thebaine is not used therapeutically itself, it can be converted industrially into a variety of therapeutically important opiate alkaloids including oxycodone, oxymorphone, nalbuphine, naloxone, naltrexone, diprenorphine, buprenorphine and etorphine. Buprenorphine, for example, is a thebaine derivative with powerful analgesia approximately twenty-five to forty times as potent as morphine, and is indicated for the treatment of moderate to severe chronic pain or for the treatment of opiate addiction.
A series of chemical reactions convert thebaine to 3-O-methyl-N-cyano-buprenorphine (whose chemical name is 6,14-ethenomorphinan-17-carbonitrile, 4,5-epoxy-18,19-dihydro-7-(1-hydroxy-1,2,2-trimethylpropyl)-3,6-dimethoxy-). A hydrolysis reaction then converts 3-O-methyl-N-cyano-buprenorphine to norbuprenorphine (whose chemical name is 6,14-ethenomorphinan-7-methanol, α-(1,1-dimethylethyl)-4,5-epoxy-18,19-dihydro-3-hydroxy-6-methoxy-α-methyl-). During the hydrolysis reaction, however, the partially hydrolyzed intermediate, 3-O-methyl-norbuprenorphine, is formed. 3-O-methyl-norbuprenorphine is an impurity that has to be removed to achieve the highest purity and yield of the product, norbuprenorphine. Since the levels of the 3-O-methyl-norbuprenorphine impurity can be as high as 10%, this step of the process significantly reduces the final yield of buprenorphine. A need therefore exists for a process to reduce the formation of 3-O-methyl-norbuprenorphine or recycle it back into the buprenorphine production process.